1. PENTOSE PHOSPHATE CYCLE
33
deficiency gene even though these culturally distinct groups are living
close to where the P. falciparum malaria is prevalent (245). In two cases
of the highland linguistic group, the frequency of the enzyme-deficiency
gene was greater than that of the lowland. Thalassemia was also found
to be dissociated from enzyme deficiency in that the former yielded a
consistent high incidence in the coastal regions, rapidly diminishing with
altitude. On the other hand, the enzyme deficiency gave erratic frequencies in the various linguistic groups examined.
How does the G-6-P DH deficiency affect the pentose phosphate
cycle? We would expect a decrease in the level of 6-phosphogluconate,
and hence less pentose phosphates via the oxidative pathway. [Primaquine-sensitive erythrocytes possess a fully active 6-phosphogluconate
dehydrogenase (246).]
In order to compensate for a low level of
pentose phosphates synthesis, more active transketolase and transaldolase
are required. This is indeed the case (247).
By comparison with the literature dealing with erythrocyte metabolism, that of leukocytic carbohydrate metabolism seems meager. The
operation of the oxidative pathway was demonstrated first in the white
cells from the peripheral blood of cats, rabbits, and dogs (248). The
metabolism of glucose via the oxidative pentose phosphate cycle is
quantitatively very small (111, 249) in normal human leukocytes. Less
than 10% of the glucose catabolized is via this pathway although somewhat higher values are obtained for myelocytic leukemia and for
lymphocytic leukemia. These values were estimated from the radioactive carbon dioxide formed from specifically labeled glucose as well
as from the specific activity of the labeled lactate. Transketolase and
transaldolase were also found in both normal and leukemic cells. Levels
of other enzymes, including G-6-P DH, 6-PG DH, and pentose phosphate
isomerase were also studied to determine the factors controlling the rate
behavior in the multienzyme systems of normal and leukemic leukocytes
(250). The activities of the two dehydrogenases along with the glycolytic
enzymes approximately parallel the over-all aerobic glycolysis as measured by lactate production, but that of pentose phosphate isomerase
remained constant in both normal and leukemic cells alike. Further
experiments in the presence and absence of ADP, ATPase, and glucose6-phosphate indicate that hexokinase is rate limiting. It may well be that
the increase in flow of glucose through the shunt mechanism is indirectly
controlled by this enzyme and that the higher percentage participation
of the pentose cycle in leukemia is due to a deficiency of hexokinase.
Specific activity of G-6-P DH based on units per cell could be misleading, however (251). Thus if the enzyme levels in myeloid leukemic cells
(granulocytes) were compared with the granulocytes in the normal
33
deficiency gene even though these culturally distinct groups are living
close to where the P. falciparum malaria is prevalent (245). In two cases
of the highland linguistic group, the frequency of the enzyme-deficiency
gene was greater than that of the lowland. Thalassemia was also found
to be dissociated from enzyme deficiency in that the former yielded a
consistent high incidence in the coastal regions, rapidly diminishing with
altitude. On the other hand, the enzyme deficiency gave erratic frequencies in the various linguistic groups examined.
How does the G-6-P DH deficiency affect the pentose phosphate
cycle? We would expect a decrease in the level of 6-phosphogluconate,
and hence less pentose phosphates via the oxidative pathway. [Primaquine-sensitive erythrocytes possess a fully active 6-phosphogluconate
dehydrogenase (246).]
In order to compensate for a low level of
pentose phosphates synthesis, more active transketolase and transaldolase
are required. This is indeed the case (247).
By comparison with the literature dealing with erythrocyte metabolism, that of leukocytic carbohydrate metabolism seems meager. The
operation of the oxidative pathway was demonstrated first in the white
cells from the peripheral blood of cats, rabbits, and dogs (248). The
metabolism of glucose via the oxidative pentose phosphate cycle is
quantitatively very small (111, 249) in normal human leukocytes. Less
than 10% of the glucose catabolized is via this pathway although somewhat higher values are obtained for myelocytic leukemia and for
lymphocytic leukemia. These values were estimated from the radioactive carbon dioxide formed from specifically labeled glucose as well
as from the specific activity of the labeled lactate. Transketolase and
transaldolase were also found in both normal and leukemic cells. Levels
of other enzymes, including G-6-P DH, 6-PG DH, and pentose phosphate
isomerase were also studied to determine the factors controlling the rate
behavior in the multienzyme systems of normal and leukemic leukocytes
(250). The activities of the two dehydrogenases along with the glycolytic
enzymes approximately parallel the over-all aerobic glycolysis as measured by lactate production, but that of pentose phosphate isomerase
remained constant in both normal and leukemic cells alike. Further
experiments in the presence and absence of ADP, ATPase, and glucose6-phosphate indicate that hexokinase is rate limiting. It may well be that
the increase in flow of glucose through the shunt mechanism is indirectly
controlled by this enzyme and that the higher percentage participation
of the pentose cycle in leukemia is due to a deficiency of hexokinase.
Specific activity of G-6-P DH based on units per cell could be misleading, however (251). Thus if the enzyme levels in myeloid leukemic cells
(granulocytes) were compared with the granulocytes in the normal